Intrauterine exposure to diabetes and risk of cardiovascular disease in adolescence and early adulthood: a population-based birth cohort study.

BACKGROUND: It is unclear whether intrauterine exposure to maternal diabetes is associated with risk factors for cardiovascular disease and related end points in adulthood. We examined this potential association in a population-based birth cohort followed up to age 35 years. METHODS: We performed a cohort study of offspring born between 1979 and 2005 (n = 293 546) and followed until March 2015 in Manitoba, Canada, using registry-based administrative data. The primary exposures were intrauterine exposure to gestational diabetes and type 2 diabetes mellitus. The primary outcome was a composite measure of incident cardiovascular disease events, and the secondary outcome was a composite of risk factors for cardiovascular disease in offspring followed up to age 35 years. RESULTS: The cohort provided 3 628 576 person-years of data (mean age at latest follow-up 20.5 [standard deviation 6.4] years, 49.3% female); 2765 (0.9%) of the offspring experienced a cardiovascular disease end point, and 12 673 (4.3%) experienced a cardiovascular disease risk factor. After propensity score matching, the hazard for cardiovascular disease end points was elevated in offspring exposed to gestational diabetes (adjusted hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.12-1.79) but not type 2 diabetes (adjusted HR 1.40, 95% CI 0.98-2.01). A similar association was observed for cardiovascular disease risk factors (gestational diabetes: adjusted HR 1.92, 95% CI 1.75-2.11; type 2 diabetes: adjusted HR 3.40, 95% CI 3.00-3.85). INTERPRETATION: Intrauterine exposure to maternal diabetes was associated with higher morbidity and risk related to cardiovascular disease among offspring up to 35 years of age.

Reduced monocyte adhesion to aortae of diabetic plasminogen activator inhibitor-1 knockout mice.

OBJECTIVE AND DESIGN: To determine the requirement of plasminogen activator inhibitor-1-knockout (PAI-1) for monocyte adhesion in animals and cells under diabetic conditions. METHODS AND SUBJECTS: Monocyte adhesion assay, enzyme-linked immunosorbent assay, and Western blotting were used in analyzing samples from PAI-1-knockout (PAI-1-KO) mice or cultured human umbilical vein endothelial cells (HUVEC). TREATMENTS: Diabetes in PAI-1-KO and wild-type mice was induced by intraperitoneal injection of streptozotocin (STZ). HUVEC was transfected with short interference RNA (siRNA) against PAI-1, tumor necrosis factor-α (TNFα), or toll-like receptor (TLR4), and then was treated with glycated low-density lipoproteins (glyLDL). RESULTS: The adhesion of monocytes to aortic intima was reduced in PAI-1-KO mice, which was associated with decreased levels of TNFα and monocyte chemotactic protein-1 (MCP-1) in plasma and cardiovascular tissue, and increased abundances of urokinase plasminogen activator (uPA) and uPA receptor (uPAR) in cardiovascular tissue compared to wild-type mice. Significant reductions in monocyte adhesion, inflammatory, and fibrinolytic regulators were detected in cardiovascular tissue or plasma in diabetic PAI-1-KO mice compared to wild-type diabetic mice. Transfection of PAI-1, TNFα or TLR4 siRNA to HUVEC inhibited glyLDL-induced monocyte adhesion to EC. PAI-1 siRNA inhibited the abundances of TLR4 and TNFα in EC. CONCLUSION: The findings suggest that PAI-1 is required for diabetes-induced monocyte adhesion via interactions with uPA/uPAR, and it also regulates TLR4 and TNFα expression in vascular EC. Inhibition of PAI-1 potentially reduces vascular inflammation under diabetic condition.

Effects of lifestyle intervention on dietary intake, physical activity level, and gestational weight gain in pregnant women with different pre-pregnancy Body Mass Index in a randomized control trial.

BACKGROUND: The objectives of this study were to assess the efficacy of lifestyle intervention on gestational weight gain in pregnant women with normal and above normal body mass index (BMI) in a randomized controlled trial. METHODS: A total of 116 pregnant women (<20 weeks of pregnancy) without diabetes were enrolled and 113 pregnant women completed the program. Participants were randomized into intervention and control groups. Women in the intervention group received weekly trainer-led group exercise sessions, instructed home exercise for 3-5-times/week during 20-36 weeks of gestation, and dietary counseling twice during pregnancy. Participants in the control group did not receive the intervention. All participants completed a physical activity questionnaire and a 3-day food record at enrolment and 2 months after enrolment. RESULTS: The participants in the intervention group with normal pre-pregnancy BMI (≤24.9 kg/M2, n = 30) had lower gestational weight gain (GWG), offspring birth weight and excessive gestational weight gain (EGWG) on pregnancy weight gain compared to the control group (n = 27, p < 0.05). Those weight related-changes were not detected between the intervention (n = 27) and control group (n = 29) in the above normal pre-pregnancy BMI participants. Intervention reduced total calorie, total fat, saturated fat and cholesterol intake were detected in women with normal or above normal pre-pregnancy BMI compared to the control group (p < 0.05 or 0.01). Increased physical activity and reduced carbohydrate intake were detected in women with normal (p < 0.05), but not above normal, pre-pregnancy BMI at 2 months after the onset of the intervention compared to the control group. CONCLUSION: The results of the present study demonstrated that the lifestyle intervention program decreased EGWG, GWG, offspring birth weight in pregnant women with normal, but not above normal, pre-pregnancy BMI, which was associated with increased physical activity and decreased carbohydrate intake. TRIAL REGISTRATION: NCT00486629.

Influence of Northern Wild Rice on Gut Dysbiosis and Short Chain Fatty Acids: Correlation with Metabolic and Inflammatory Markers in Mice on High Fat Diet.

Wild rice (WLD) attenuated hyperglycemia, hyperlipidemia and chronic inflammation in mice receiving a high-fat diet (HFD) versus white rice (WHR), but the underlying mechanism is not well understood. We examined the influence of HFD + WLD on gut microbiota, short chain fatty acids (SCFAs) and the correlation with metabolic or inflammatory markers in mice versus HFD + WHR. C57BL/6J mice received HFD + 26 g weight (wt) % WHR or WLD or 13 g wt% WHR + 13 g wt% WLD (WTWD) for 12 weeks. Plasma levels of glucose, cholesterol and triglycerides, insulin resistance and inflammatory markers after overnight fasting were lower, and the abundances of fecal Lactobacillus gasseri and propionic acid were higher in HFD + WLD-fed mice than in HFD + WHR-fed mice. The anti-inflammatory effects of HFD + WTWD were weaker than HFD + WLD but were greater than those in HFD + WHR-fed mice. Abundances of fecal Lactobacillus gasseri and propionic acid in mice receiving HFD + WLD were higher than those in mice fed with HFD + WHR. The abundances of fecal L. gasseri and propionic acid negatively correlated with metabolic and inflammatory markers. The findings of the present study suggest that WLD attenuated metabolic and inflammatory disorders in mice on HFD. Interactions between WLD components and gut microbiota may upregulate fecal SCFAs, and the latter may be attributed to the benefits of WLD on metabolism and inflammation in mice on HFD.

Effects of glycated low-density lipoprotein on cell viability, proliferation, and growth factors of mouse embryo fibroblasts.

The predominant cause of death in diabetic patients is atherosclerotic coronary artery disease (CAD). Major gross cellular changes in the vascular wall of persons with CAD include endothelial injury and foam cell formation, as well as smooth muscle cell and fibroblast proliferation. This study examined the effects of glycated low density lipoprotein (glyLDL), a biochemical marker of diabetes, on cell viability, proliferation, and the expression of multiple growth factors in mouse embryo fibroblasts (MEF). The results demonstrated that exposure to ≥150 µg/mL of glyLDL for 24 h or 100 µg/mL of glyLDL for ≥48 h either significantly reduced cell viability or increased DNA fragmentation in MEF. GlyLDL treatment (25-100 µg/mL for up to 12 h) significantly increased the abundance of proliferating cell nuclear antigen (PCNA) and achieved a peak after 4 h exposure to glyLDL. Abundances of fibroblast growth factor-basic (FGF), transforming growth factor-ß (TGF), and platelet-derived growth factor-A (PDGF) in MEF reached maximal levels after 2 h exposure to 50 µg/mL of glyLDL. The maximal increase of vascular endothelial growth factor (VEGF) was detected in MEF after 4 h of exposure to 50 µg/mL of glyLDL. Inhibitors for FGF (AZD4547), VEGF, or PDGF receptors (Axitinib), but not that for TGF receptor (LY364947), significantly decreased the abundance of (PCNA) in endothelial cells. The findings suggest that early exposure to a low dosage of glyLDL transiently increases the proliferation of MEF through the upregulation of FGF, VEGF, and (or) PDGF, and prolonged exposure to high concentrations of glyLDL reduced cell viability, which possibly accelerates atherogenesis under diabetic condition.

Special Issue "Nutritional Regulation on Gut Microbiota": Editorial.

Accumulated lines of evidence demonstrate that the gut microbiota plays a critical role in metabolism, inflammation and the pathophysiology of many chronic diseases [...].

Impact of anthocyanin component and metabolite of Saskatoon berry on gut microbiome and relationship with fecal short chain fatty acids in diet-induced insulin resistant mice.

Previous studies demonstrated that oral administration of Saskatoon berry powder (SBp) reduced fasting plasma glucose (FPG), insulin resistance, lipids, and inflammatory markers in diet-induced insulin resistant rodents. Mechanism for the beneficial effects of SB remains unclear. The present study examined the effects of high fat-high sucrose (HFHS) diet supplemented with or without 5% SBp, cyanidin-3-glucoside (C3G, an anthocyanin rich in SBp) at a dosage of C3G in 5% SBp, or equimolar concentration of protocatechuic acid (PCA, a relatively stable metabolite of C3G) for 11 weeks on FPG, cholesterol, triglycerides, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), circulatory inflammatory markers, fecal microbiota, and short chain fatty acids in mice. HFHS diet significantly enhanced FPG, insulin, HOMA-IR, lipids and inflammatory markers, but reduced the abundance of fecal Bacteroidetes, Muribaculaceae and propionate compared to low fat diet. Supplementation of SBp, C3G or PCA significantly attenuated HFHS diet induced metabolic and inflammatory markers, and increased the abundances of fecal Muribaculaceae and propionate compared to HFHS diet alone. The abundances of fecal Muribaculaceae negatively correlated with FPG, lipids, HOMA-IR and inflammatory markers in the mice. The abundances of fecal propionate positively correlated with fecal Muribaculaceae and negatively correlated with the metabolic and inflammatory markers. The findings suggest that C3G in SBp and PCA contribute to the metabolic and anti-inflammatory effect of SBp in mice. The increases in fecal Muribaculaceae and propionate may play important regulatory roles in the anti-diabetic and anti-inflammatory benefits of SBp, C3G, and PCA in mice.

Influence of Brown or Germinated Brown Rice Supplementation on Fecal Short-Chain Fatty Acids and Microbiome in Diet-Induced Insulin-Resistant Mice.

Intake of whole grain foods is associated with improving metabolic profile compared to refined grain products, but the underlying mechanism remains unclear. The present study examined the effects of brown rice (BRR) or germinated brown rice (GBR) supplementation on fecal short-chain fatty acids (SCFAs), and relationship with gut microbiota, metabolism and inflammation in high fat (HF)-diet-fed mice. The results demonstrated that an HF diet supplemented with BRR or GBR comparably increased the abundance of fecal isobutyric acid compared to that in mice receiving HF+white rice (WHR) diet (p < 0.01). The abundance of valeric acid in HF+GBR-diet-fed mice was higher than those receiving HF+WHR diet (p < 0.05). The abundances of fecal isobutyric acid negatively correlated with fasting plasma glucose, insulin, cholesterol, triglycerides, tumor necrosis factor-α, plasminogen activator inhibit-1, monocyte chemotactic protein-1 and homeostatic model assessment of insulin resistance (p < 0.01). The abundance of valeric acids negatively correlated with insulin resistance (p < 0.05). The abundances of isobutyric acid positively correlated with Lactobacillus, but negatively correlated with Dubosiella genus bacteria (p < 0.05). The findings demonstrated that the increases in SCFAs in the feces of BRR and GBR-treated mice were associated with improvements in gut microbiome, metabolic and inflammatory profile, which may contribute to the antidiabetic and anti-inflammatory effects of the whole grains in HF-diet-fed mice.

SmartMoms Canada: An evaluation of a mobile app intervention to support a healthy pregnancy.

BACKGROUND: There is a lack of cost-effective and readily available access to evidence-based information to manage healthy behaviours for pregnant individuals. Mobile health (mHealth) tools offer a cost-effective, interactive, personalized option that can be delivered anywhere at a time most convenient for the user. This study protocol was primarily developed to, i) assess the feasibility of the SmartMoms Canada intervention in supporting participants to achieve gestational weight gain (GWG) guidelines. The secondary objectives are to, ii) assess user experience with the app, measured by adherence to the program via app software metrics and frequency of use, iii) determine the impact of SmartMoms Canada app usage on the adoption of healthful behaviours related to nutrition, physical activity and sleep habits, improvements in health-related quality of life, pregnancy-related complications, and symptoms of depression, and iv) investigate the potential extended effects of the app on postpartum health-related outcomes. METHODS: This is a feasibility trial. Pregnant individuals aged 18-40 years with pre-gravid body mass index between 18.5 and 39.9 kg/m2, carrying a singleton fetus, having Wi-Fi access, and at ≤20 weeks' gestation will be recruited. Eligible people will be followed from recruitment until 12 months postpartum. DISCUSSION: SmartMoms Canada is the first bilingual Canadian-centric app designed for pregnant people. This mHealth intervention, with its ability to supply frequent interactions, provides pregnancy- related health knowledge to users, potentially leading to an improvement in pregnancy-related outcomes and behaviours, and, ultimately a reduction in the present economic burden related to in-person interventions. TRIAL REGISTRATION: ISRCTN, ISRCTN16254958. Registered 20 December 2019, http://www.isrctn.com/ ISRCTN16254958.

Impact of cyanidin-3-glucoside on glycated LDL-induced NADPH oxidase activation, mitochondrial dysfunction and cell viability in cultured vascular endothelial cells.

Elevated levels of glycated low density lipoprotein (glyLDL) are frequently detected in diabetic patients. Previous studies demonstrated that glyLDL increased the production of reactive oxygen species (ROS), activated NADPH oxidase (NOX) and suppressed mitochondrial electron transport chain (mETC) enzyme activities in vascular endothelial cells (EC). The present study examined the effects of cyanidin-3-glucoside (C3G), a type of anthocyanin abundant in dark-skinned berries, on glyLDL-induced ROS production, NOX activation and mETC enzyme activity in porcine aortic EC (PAEC). Co-treatment of C3G prevented glyLDL-induced upregulation of NOX4 and intracellular superoxide production in EC. C3G normalized glyLDL-induced inhibition on the enzyme activities of mETC Complex I and III, as well as the abundances of NADH dehydrogenase 1 in Complex I and cytochrome b in Complex III in EC. Blocking antibody for the receptor of advanced glycation end products (RAGE) prevented glyLDL-induced changes in NOX and mETC enzymes. Combination of C3G and RAGE antibody did not significantly enhance glyLDL-induced inhibition of NOX or mETC enzymes. C3G reduced glyLDL-induced RAGE expression with the presence of RAGE antibody. C3G prevented prolonged incubation with the glyLDL-induced decrease in cell viability and the imbalance between key regulators for cell viability (cleaved caspase 3 and B cell Lyphoma-2) in EC. The findings suggest that RAGE plays an important role in glyLDL-induced oxidative stress in vascular EC. C3G may prevent glyLDL-induced NOX activation, the impairment of mETC enzymes and cell viability in cultured vascular EC.

Effect of selenium biofortification on bioactive compounds and antioxidant activity in germinated black soybean.

Biofortification using inorganic selenium has become an effective strategy to enhance selenium content in crops. In the present study, the effects of selenium biofortification on the chemical composition and antioxidant capacity of black soybean (BS) during germination were studied. The contents of selenium, total sugar, vitamin C, γ-aminobutyric acid, total polyphenols, and total flavonoids in selenium biofortified germinated black soybeans (GBS-Se) significantly increased compared to germinated black soybeans (GBS). However, the contents of soluble protein, fat, and reducing sugar were decreased, while fatty acid composition was not significantly different between GBS and BS. HPLC analysis showed that 12 phenolic acids of all samples, which mainly existed in free forms. Their contents increased at low concentration of selenium and decreased along with the rise of selenium concentrations. The antioxidant activity of GBS-Se as analyzed by Pearson correlation analysis positively correlated with the accumulation of phenolic substances. Principal component analysis (PCA) showed that GBS and GBS-Se were significantly different from BS. Moreover, the physicochemical indexes of GBS showed regularly changes with increasing selenium content, and those of GBS-Se50 and GBS-Se75 were significantly different from GBS. The results provide a systematic evaluation on the effect of selenium fortification on the germination of seeds and useful information for the development of Se-enriched functional foods. PRACTICAL APPLICATION: The organic selenium black soybean (BS) produced by the germination method can be directly processed and eaten to improve human health. In addition, complexes of organic selenium, vitamin C, and γ-aminobutyric acid of germinated BS can be developed into functional substances and applied to food or health products as functional ingredient and/or natural antioxidant supplements.

The short-term effect of a mHealth intervention on gestational weight gain and health behaviors: The SmartMoms Canada pilot study.

Gestational weight gain (GWG) has been shown to impact several maternal-infant outcomes. Since healthcare provider guidance on weight gain and healthy behaviors alone has failed to help women to meet guidelines during pregnancy, a practical adjunctive approach is to deliver evidence-based behavior change programs through mobile interventions. The present study aimed to assess the short-term effect of the SmartMoms Canada app to promote adequate GWG and healthy behaviors. Twenty-nine pregnant women were recruited in this app-based intervention trial to test whether a higher app usage (≥ 3.8 min·week-1) between 12-20 gestational weeks and 24-28 gestational weeks improved GWG, diet, physical activity, and sleep, compared to women with a lower app usage (< 3.8 min·week-1). Two-way mixed ANOVA for repeated measures was used to estimate the effect of the app usage and time, as well as their interaction on GWG and healthy behaviors. The likelihood ratio was used to examine the association between app usage categorization and GWG classification. Cramer's V statistic was used to estimate the effect size for interpretation of the association. Pregnant women using the SmartMoms Canada app more frequently had a higher moderate-to-vigorous physical activity (MVPA) daily average when compared with women with a lower usage (mean difference: 17.84 min/day, 95% CI: 2.44; 33.25). A moderate effect size (28.6% vs. 15.4%; Cramer's V = 0.212) was found for the association between app categorization and rate of GWG, representing a greater adherence to the GWG guidelines in women in the higher app usage group vs. the lower app usage group. Considering other physical activity, diet, and sleep variables, no app categorization effect was observed. A short-term higher usage of SmartMoms Canada app has a positive effect on objectively-measured MVPA.

Impact of Germinated Brown Rice and Brown Rice on Metabolism, Inflammation, and Gut Microbiome in High Fat Diet-Induced Insulin Resistant Mice.

The constituents of germinated brown rice (GBR), brown rice (BRR), and white rice (WHR) and their impact on metabolism, inflammation, and gut microbiota in high fat (HF) diet-fed mice were examined. The contents of total fiber and γ-aminobutyric acid in BRR and GBR were higher than that in WHR (p < 0.05). Male C57 BL/6J mice received HF diet+26 g% of WHR, BRR, or GBR for 12 weeks. BRR and GBR comparably reduced HF diet-induced increases in fasting plasma glucose, lipids, insulin resistance, and inflammatory markers compared to WHR (p < 0.01). The abundance of fecal Bacteroidetes in mice fed HF+GBR or HF+BRR was higher than in HF+WHR-fed mice (p < 0.05). The abundance of fecal Lactobacillus gasseri in GBR-fed mice was greater than that in WHR- or BRR-fed mice (p < 0.05). The results indicated that GBR or BRR attenuated hyperglycemia, insulin resistance, and inflammation in mice. HF+GBR, but not HF+BRR, increased a probiotic bacteria in the gut.

Persistent pulmonary hypertension results in reduced tetralinoleoyl-cardiolipin and mitochondrial complex II + III during the development of right ventricular hypertrophy in the neonatal pig heart.

Persistent pulmonary hypertension of the newborn (PPHN) results in right ventricular (RV) hypertrophy followed by right heart failure and an associated mitochondrial dysfunction. The phospholipid cardiolipin plays a key role in maintaining mitochondrial respiratory and cardiac function via modulation of the activities of enzymes involved in oxidative phosphorylation. In this study, changes in cardiolipin and cardiolipin metabolism were investigated during the development of right heart failure. Newborn piglets (<24 h old) were exposed to a hypoxic (10% O(2)) environment for 3 days, resulting in the induction of PPHN. Two sets of control piglets were used: 1) newborn or 2) exposed to a normoxic (21% O(2)) environment for 3 days. Cardiolipin biosynthetic and remodeling enzymes, mitochondrial complex II + III activity, incorporation of [1-(14)C]linoleoyl-CoA into cardiolipin precursors, and the tetralinoleoyl-cardiolipin pool size were determined in both the RV and left ventricle (LV). PPHN resulted in an increased heart-to-body weight ratio, RV-to-LV plus septum weight ratio, and expression of brain naturetic peptide in RV. In addition, PPHN reduced cardiolipin biosynthesis and remodeling in the RV and LV, which resulted in decreased tetralinoleoyl-cardiolipin levels and reduced complex II + III activity and protein levels of mitochondrial complexes II, III, and IV in the RV. This is the first study to examine the pattern of cardiolipin metabolism during the early development of both the RV and LV of the newborn piglet and to demonstrate that PPHN-induced alterations in cardiolipin biosynthetic and remodeling enzymes contribute to reduced tetralinoleoyl-cardiolipin and mitochondrial respiratory chain function during the development of RV hypertrophy. These defects in cardiolipin may play an important role in the rapid development of RV dysfunction and right heart failure in PPHN.

Dose-Responses Relationship in Glucose Lowering and Gut Dysbiosis to Saskatoon Berry Powder Supplementation in High Fat-High Sucrose Diet-Induced Insulin Resistant Mice.

Administration of freeze-dried powder of Saskatoon berry (SB), a popular fruit enriched with antioxidants, reduced glucose level, inflammatory markers and gut microbiota disorder in high fat-high sucrose (HFHS) diet-induced insulin resistant mice. The present study examined the dose-response relationship in metabolic, inflammatory and gut microbiotic variables to SB power (SBp) supplementation in HFHS diet-fed mice. Male C57 BL/6J mice were fed with HFHS diet supplemented with 0, 1%, 2.5% or 5% SBp for 11 weeks. HFHS diet significantly increased the levels of fast plasma glucose (FPG), cholesterol, triglycerides, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), tumor necrosis factor-α, monocyte chemotactic protein-1 and plasminogen activator inhibitor-1, but decreased fecal Bacteroidetes phylum bacteria and Muribaculaceae family bacteria compared to low fat diet. SBp dose-dependently reduced metabolic and inflammatory variables and gut dysbiosis in mice compared with mice receiving HFHS diet alone. Significant attenuation of HFHS diet-induced biochemical disorders were detected in mice receiving ≥1% SBp. The abundances of Muribaculaceae family bacteria negatively correlated with body weights, FPG, lipids, insulin, HOMA-IR and inflammatory markers in the mice. The results suggest that SBp supplementation dose-dependently attenuated HFHS diet-induced metabolic and inflammatory disorders, which was associated with the amelioration of gut dysbiosis in the mice.

Saskatoon berry powder reduces hepatic steatosis and insulin resistance in high fat-high sucrose diet-induced obese mice.

Non-alcoholic fatty liver disease is a common metabolic disorder associated with insulin resistance and lacks a specific treatment. Our previous studies demonstrated that freeze-dried Saskatoon berry powder (SBp) reduced high fat-high sucrose (HFHS) diet-induced hyperglycemia and insulin resistance in mice. The present study examined the effect of SBp and one of its active components, cyanidin-3-glucoside (C3G), on hepatic steatosis in mice fed with HFHS diet for 10 weeks. HFHS diet significantly increased fasting plasma glucose, cholesterol, triglycerides, insulin resistance, inflammatory markers (tumor necrosis factor-α, monocyte chemotactic protein-1, plasminogen activator inbitor-1), alanine aminotransferase activity, and monocyte adhesion compared to control diet. In the liver, HFHS diet increased steatosis, lipid accumulation, collagen deposition, and the abundance of patatin-like phospholipase domain-containing 3, CCAAT-enhancer-binding protein homologous protein, toll-like receptor-4, and macrophage marker. Supplementation with SBp (5%) or C3G in an amount corresponding to that in 5% SBp to HFHS diet had similar effects to reduced fasting plasma glucose, liver steatosis, enzyme activity, lipid, collagen and macrophage deposition, hyperglycemia, hyperlipidemia, insulin resistance, monocyte adhesion, markers related to liver steatosis, inflammation, oxidative or endoplasmic reticulum stress in the peripheral circulation and/or liver compared to mice fed with HFHS diet alone. No significant difference in the studied variables was detected between mice treated with HFHS+SBp and C3G diet. The results suggest that SBp or C3G administration attenuates HFHS diet-induced liver steatosis in addition to insulin resistance and chronic inflammation in mice. C3G may contribute to the beneficial effects of SBp.

Impact of remote prenatal education on program participation and breastfeeding of women in rural and remote Indigenous communities.

BACKGROUND: First Nations (FN) women have a higher risk of diabetes than non-FN women in Canada. Prenatal education and breastfeeding may reduce the risk of diabetes in mothers and offspring. The rates of breastfeeding initiation and participation in the prenatal program are low in FN communities. METHODS: A prenatal educational website, social media-assisted prenatal chat groups and community support teams were developed in three rural or remote FN communities in Manitoba. The rates of participation of pregnant women in prenatal programs and breastfeeding initiation were compared before and after the start of the remote prenatal education program within 2014-2017. FINDINGS: The participation rate of FN pregnant women in rural or remote communities in the prenatal program and breastfeeding initiation during 1-year after the start of the community-based remote prenatal education program were significantly increased compared to that during 1-year before the start of the program (54% versus 36% for the participation rate, 50% versus 34% for breastfeeding initiation, p < 0·001). Availability of high-speed Wi-Fi and/or postpartum supporting team were associated with favorite study outcomes. Positive feedback on the remote prenatal education was received from participants. INTERPRETATION: The findings suggest that remote prenatal education is feasible and effective for improving the breastfeeding rate and engaging pregnant women to participate in the prenatal program in rural or remote FN communities. The remote prenatal education remained active during COVID-19 in the participating communities, which suggests an advantage to expand remote prenatal education in other Indigenous communities. FUNDING: Canadian Institutes of Health Research, the Lawson Foundation and University of Manitoba.

Effects of extensively oxidized low-density lipoprotein on mitochondrial function and reactive oxygen species in porcine aortic endothelial cells.

Atherosclerotic cardiovascular disease is the leading cause of mortality in the Western world. Dysfunction of the mitochondrial respiratory chain and overproduction of reactive oxygen species (ROS) are associated with atherosclerosis and cardiovascular disease. Oxidation increases the atherogenecity of LDL. Oxidized LDL may be apoptotic or nonapoptotic for vascular endothelial cells (EC), depending on the intensity of oxidation. A previous study demonstrated that nonapoptotic oxidized LDL increased activity of mitochondrial complex I in human umbilical vein EC. The present study examined the impact of extensively oxidized LDL (eoLDL) on oxygen consumption and the activities of key enzymes in the mitochondrial respiratory chain of cultured porcine aortic EC. Oxygraphy detected that eoLDL significantly reduced oxygen consumption in various mitochondrial complexes. Treatment with eoLDL significantly decreased NADH-ubiquinone dehydrogenase (complex I), succinate cytochrome c reductase (complex II/III), ubiquinone cytochrome c reductase (complex III), and cytochrome c oxidase (complex IV) activities and the NAD+-to-NADH ratio in EC compared with mildly oxidized LDL, LDL, or vehicle. Butylated hydroxytoluene, a potent antioxidant, normalized eoLDL-induced reductions in complex I and III enzyme activity in EC. Mitochondria-associated intracellular ROS and release of ROS from EC were significantly increased after eoLDL treatment. These findings suggest that eoLDL impairs enzyme activity in mitochondrial respiratory chain complexes and increases ROS generation from mitochondria of arterial EC. Collectively, these effects could contribute to vascular injury and atherogenesis under conditions of hypercholesterolemia and oxidative stress.

Effect of hirulog-like peptide on balloon catheter injury-induced neointimal formation in femoral arteries of minipigs and relationship with inflammatory mediators.

Vascular intervention-induced neointimal formation is a major drawback for managing atherosclerotic cardiovascular diseases using invasive vascular procedures. Our previous studies demonstrated that hirulog-like peptide (HLP) reduced balloon catheter dilation-induced neointimal formation or restenosis in carotid arteries of rats or atherosclerotic rabbits with less interruption in coagulation or bleeding than heparin or hirulog-1. The present study examined the effect of HLP on balloon catheter injury-induced neointimal formation in femoral arteries of minipigs. Intravenous infusion of HLP (1.6 mg/kg/h for 4 h started 0.5 h before the intervention) or unfractured heparin (50 U/kg/h for 4 h) significantly reduced neointimal formation in femoral arteries 4 weeks after intervention compared with the vehicle. Heparin, but not HLP, significantly prolonged activated partial thromboplastin time. HLP or heparin significantly reduced vascular intervention-induced increases in C-reactive protein, P-selectin and interleukin-6 in serum. HLP, but not heparin, normalized vascular injury-induced increase in P-selectin in platelets. The results of the present study suggest that HLP is an effective agent for preventing balloon catheter injury-induced neointimal formation in femoral arteries of minipigs. The beneficial effects of HLP on vascular injury-induced neointimal formation may partially result from its inhibition on inflammatory mediators.

Oxidative stress and diabetic cardiovascular disorders: roles of mitochondria and NADPH oxidase.

Cardiovascular diseases are the predominant cause of death in patients with diabetes mellitus. Underlying mechanism for the susceptibility of diabetic patients to cardiovascular diseases remains unclear. Elevated oxidative stress was detected in diabetic patients and in animal models of diabetes. Hyperglycemia, oxidatively modified atherogenic lipoproteins, and advanced glycation end products are linked to oxidative stress in diabetes. Mitochondria are one of major sources of reactive oxygen species (ROS) in cells. Mitochondrial dysfunction increases electron leak and the generation of ROS from the mitochondrial respiratory chain (MRC). High levels of glucose and lipids impair the activities of MRC complex enzymes. NADPH oxidase (NOX) generates superoxide from NADPH in cells. Increased NOX activity was detected in diabetic patients. Hyperglycemia and hyperlipidemia increased the expression of NOX in vascular endothelial cells. Accumulated lines of evidence indicate that oxidative stress induced by excessive ROS production is linked to many processes associated with diabetic cardiovascular complications. Overproduction of ROS resulting from mitochondrial dysfunction or NOX activation is associated with uncoupling of endothelial nitric oxide synthase, which leads to reduced production of nitric oxide and endothelial-dependent vasodilation. Gene silence or inhibitor of NOX reduced oxidized or glycated LDL-induced expression of plasminogen activator inhibitor-1 in endothelial cells. Statins, hypoglycemic agents, and exercise may reduce oxidative stress in diabetic patients through the reduction of NOX activity or the improvement of mitochondrial function, which may prevent or postpone the development of cardiovascular complications.